Models were developed to quantify the risk of deoxynivalenol (DON) contamination of maize grain based on weather, cultural practices, hybrid resistance, and Gibberella ear rot (GER) intensity. Data on natural DON contamination of 15 to 16 hybrids and weather were collected from 10 Ohio locations over 4 years. Logistic regression with 10-fold cross-validation was used to develop models to predict the risk of DON ≥1 ppm. The presence and severity of GER predicted DON risk with an accuracy of 0.81 and 0.87, respectively. Temperature, relative humidity, surface wetness, and rainfall were used to generate 37 weather-based predictor variables summarized over each of six 15-day windows relative to maize silking (R1). With these variables, least absolute shrinkage and selection operator (LASSO) followed by all-subsets variable selection and logistic regression with 10-fold cross-validation were used to build single-window weather-based models, from which 11 with one or two predictors were selected based on performance metrics and simplicity. LASSO logistic regression was also used to build more complex multiwindow models with up to 22 predictors. The performance of the best single-window models was comparable to that of the best multiwindow models, with accuracy ranging from 0.81 to 0.83 for the former and 0.83 to 0.87 for the latter group of models. These results indicated that the risk of DON ≥1 ppm can be accurately predicted with simple models built using temperature- and moisture-based predictors from a single window. These models will be the foundation for developing tools to predict the risk of DON contamination of maize grain.